HDAC6

Chr Xp11.23

histone deacetylase 6

Aliases:: KIAA0901, JM21, HD6, FLJ16239, PPP1R90
MANE:: ENST00000334136.11

OMIM: 300272 ↗NCBI: 10013 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

HDAC6 · Q9UBN7

v62025-08-01

Predicted Aligned Error matrix for HDAC6 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.8/ 100

Confident

1,215 residues

Confidence breakdown

Very high(≥ 90)64%
Confident(70–90)4%
Low(50–70)3%
Very low(< 50)30%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
Unknown
Hydrocephalus
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Anophthalmia or microphthalmia
Intellectual disability
Structural eye disease
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Disease associations (Open Targets)

X-linked dominant chondrodysplasia, Chassaing-Lacombe type
0.59
plasma cell myeloma
0.57
primary cutaneous T-cell non-Hodgkin lymphoma
0.57
neoplasm
0.57
Duchenne muscular dystrophy
0.52
T-cell non-Hodgkin lymphoma
0.52
peripheral T-cell lymphoma, not otherwise specified
0.52
mature T-cell and NK-cell non-Hodgkin lymphoma
0.50
breast cancer
0.39
neurodegenerative disease
0.39

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Protein deacetylase HDAC6

Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:38534334, PubMed:39567688). Plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (PubMed:12024216, PubMed:20308065, PubMed:26246421). Required for cilia disassembly via deacetylation of alpha-tubulin (PubMed:17604723, PubMed:26246421). Alpha-tubulin deacetylation results in destabilization of dynamic microtubules (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Deacetylates SQSTM1 (PubMed:31857589). Deacetylates peroxiredoxins PRDX1 and PRDX2, decreasing their reducing activity (PubMed:18606987). Deacetylates antiviral protein RIGI in the presence of viral mRNAs which is required for viral RNA detection by RIGI (By similarity). Sequentially deacetylates and polyubiquitinates DNA mismatch repair protein MSH2 which leads to MSH2 degradation, reducing cellular sensitivity to DNA-damaging agents and decreasing cellular DNA mismatch repair activities (PubMed:24882211). Deacetylates DNA mismatch repair protein MLH1 which prevents recruitment of the MutL alpha complex (formed by the MLH1-PMS2 heterodimer) to the MutS alpha complex (formed by the MSH2-MSH6 heterodimer), leading to tolerance of DNA damage (PubMed:30770470). Deacetylates RHOT1/MIRO1 which blocks mitochondrial transport and mediates axon growth inhibition (By similarity). Deacetylates transcription factor SP1 which leads to increased expression of ENG, positively regulating angiogenesis (PubMed:38534334). Deacetylates KHDRBS1/SAM68 which regulates alternative splicing by inhibiting the inclusion of CD44 alternate exons (PubMed:26080397). Deacetylates PRDM16 (By similarity). Acts as a valine sensor by binding to valine through the primate-specific SE14 repeat region (PubMed:39567688). In valine deprivation conditions, translocates from the cytoplasm to the nucleus where it deacetylates TET2 which promotes TET2-dependent DNA demethylation, leading to DNA damage (PubMed:39567688). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (By similarity). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (PubMed:17846173). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and targets them to the aggresome, facilitating their clearance by autophagy (PubMed:17846173). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532)